SARS-Cov-2 infection at the animal-human interface: longevity and re-infection dynamics with virus evolution
Lead Research Organisation:
ANIMAL AND PLANT HEALTH AGENCY
Department Name: Virology
Abstract
SARS-CoV-2 infection causes asymptomatic through severe clinical presentations in humans. Parameters around infection and transmission dynamics have been studied in animal models. However, there are growing reports of 'reactivation' and re-infection with variant SARS-CoV-2 viruses, months after 'recovery'. The frequency, timing, clinical and virological consequence, in terms of infectious virus shedding and onward transmission following secondary intra- and inter-species infections, remain unknown. The underlying immunological mechanisms behind these infections also remain unexplored. Additionally, SARS-CoV-2 infection in mink has generated novel virus variants, capable of infecting and partially evading existing immunity in humans, increasing the threats of re-infection. Here, we propose to use our established ferret model of SARS-CoV-2 (human and animal adapted viruses), to study longitudinal outcomes of respiratory droplet infection for two genetically different viruses over a six-month period. We will monitor virological and immunological progression of longitudinal SARS-CoV-2 infection; investigate the consequences of SARS-CoV-2 re-infection with homologous and heterologous strains; and investigate the effect of adaptation and immunity on the evolution of SARS-CoV-2 during these infections. We hypothesise that productive re-infection with SARS-CoV-2 variants can result in both infected and infectious stages, the latter being able to transmit disease irrespective of prior exposure and immune status.
These investigations will provide detailed robust novel information relevant to mitigation strategies such as droplet avoidance, herd immunity, vaccination and virus evolution. It will also address questions regarding the emergence and maintenance of SARS-CoV-2 in animal reservoirs which may threaten eradication and long-term management of COVID
These investigations will provide detailed robust novel information relevant to mitigation strategies such as droplet avoidance, herd immunity, vaccination and virus evolution. It will also address questions regarding the emergence and maintenance of SARS-CoV-2 in animal reservoirs which may threaten eradication and long-term management of COVID
Organisations
- ANIMAL AND PLANT HEALTH AGENCY (Lead Research Organisation)
- Department For Environment, Food And Rural Affairs (DEFRA) (Collaboration)
- Health and Safety Executive (Collaboration)
- Royal Veterinary College (RVC) (Collaboration)
- UNIVERSITY OF LIVERPOOL (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
Publications
James J
(2022)
Infectious droplet exposure is an inefficient route for SARS-CoV-2 infection in the ferret model.
in The Journal of general virology
| Description | SARS-CoV-2 infection causes varied clinical presentation in humans and animals ranging from asymptomatic to severe disease. Infection and transmission dynamics have been studied yet the extent primary infection protects against longitudinal re-infection with a similar or more distant virus variants remains poorly defined. The consequence of SARS-CoV-2 re-infection, ability for onward transmission and the role of antibody responses on SARS-CoV-2 virus evolution was investigated in a mild/asymptomatic ferret model. Ferrets, like mink and other mammals (cats, dogs, zoo animals, wildlife) are also fully susceptible to infection in nature. Ferrets were directly infected with either SARS-CoV-2 Delta or Omicron (BA.1.17) variant and then re-infected after five months with the same or the alternative virus. Clinical, virological and immunological parameters were assessed. Upper respiratory (nose/mouth) and gastro-intestinal (anal) shedding was observed from all directly infected previously naïve/non-immune ferrets with higher virus shedding from the Delta variant infected ferrets compared to that of those infected by Omicron. Antibodies able to inhibit the virus were high in Delta virus infected ferrets (>90) and this correlated with protective immunity against teh same or different variant re-infection. Ferrets directly infected with Omicron virus variant resulted in lower inhibitory antibody levels with limited re-infection following challenge with the same virus (omicon). However, ferrets infected with Omicron with very low antibody levels (=8) prior to re-infection were not protected against the opposite virus variant challenge and resulted in direct-contact transmission of virus ferret-to-ferret. This study demonstrated that inhibitory antibody levels can be sustained for up to five months in ferrets and provides protective immunity against re-infection with the same or a different virus variant. This supportive evidence for longitudinal immunity against re-infection and transmission contributes to our understanding on the threats of novel SARS-CoV-2 variants with regards to prior exposure, 'herd' immunity and vaccination strategies. It has relevance for ferrets, other related animal species and reflect that seen humans. |
| Exploitation Route | COVIRN project Defra R&D UK-ICN - Animal CoVs Conferences NCS-Protect Microbiology Society Annual meeting 2023 STAR-IDAZ gap analysis and roadmap for animal coronaviruses Manuscript in preparation - |
| Sectors | Agriculture Food and Drink Environment Healthcare Government Democracy and Justice |
| Description | Impact Case Study by APHA and external contractor Contribution to Defra policy and evidence notes for SARS-CoV-2 in animals |
| First Year Of Impact | 2021 |
| Sector | Environment,Healthcare |
| Impact Types | Policy & public services |
| Description | Co-ordinator in the Coronavirus in Animals gap analysis and roadmap workshop and State of the Art report for WOAH and STAR-IDAZ |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Description | SARS-CoV-2 in ferrets risk assessment |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Description | Coronavirus detection characterisation and pathogen investigation in animlas |
| Amount | £600,000 (GBP) |
| Funding ID | SE0575 |
| Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2023 |
| End | 03/2026 |
| Title | Virus stocks SARS CoV-2 (2023) |
| Description | Coronavirus stocks have been made available to the community via EVA Global https://www.european-virus-archive.com/ |
| Type Of Material | Biological samples |
| Year Produced | 2023 |
| Provided To Others? | No |
| Impact | Coronavirus stock from animals made available via the EVA Global portal |
| Title | Virus stocks - SARS-CoV-2 |
| Description | SARS-CoV-2 virus stocks made available to other researchers via EVAGlobal https://www.european-virus-archive.com/ |
| Type Of Material | Biological samples |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | Sharing of biobank materials |
| Description | Defra Investigating zoonotic and reverse-zoonotic transmission of SARS-CoV-2 |
| Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | R&D, SARS CoV-2 in animals National Reference Laboratory for SARS COV2 in animals - competent authority testing and reporting |
| Collaborator Contribution | Animal and OneHeatlh policy, HAIRS, SAGE, NERVTAG |
| Impact | Publications - Virology, Pathology, Epidemiology, Wildlife, Veterinary Abstracts, project reports 2021, 2022 Presentations - MVNA Workshop Sept 2021 MNVA JMM editorial review June 2022 |
| Start Year | 2020 |
| Description | Defra New and Emerging Disease SARS-2 in Companion Animals SE0568 and SV3700 Disease Surveillance |
| Organisation | Royal Veterinary College (RVC) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Characterisation of SARS-CoV-2 variants at the animal-human interface e.g. COVID positive households |
| Collaborator Contribution | RNA Seq genome analyses and differential diagnostics for companion animal Coronaviruses |
| Impact | Defra SARS-CoV-2 Science day Defra Final report, April 2023 |
| Start Year | 2022 |
| Description | Defra SARS-CoV-2 infection at the animal-human interface: longevity and re-infection dynamics with virus evolution |
| Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Research Integration and preparedness (COVID19JIP) COVRIN. One Health research integration on SARS-CoV-2 emergence, risk assessment and preparedness. New and Emerging Disease investigations for Coronaviruses in wildlife - deer and bats |
| Collaborator Contribution | European Joint Project partners - https://onehealthejp.eu/projects/integrative/jip-covrin Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in December 2019. COVID-19 has since spread rapidly, evolving into a pandemic with unprecedented societal and economic impact. A main focus of the COVRIN project is to reinforce collaboration and integration of research activities on SARS-CoV-2. This project aims to integrate coronavirus research activities of all project partners. The project has two main operational objectives: To identify the drivers for the emergence and spread of SARS-CoV-2. To generate data and build models for risk assessment of SARS-CoV-2. Activities to connect with stakeholders and avoid overlaps with other projects are a key focus and the project is split into four key research activities: Research on detection of SARS-CoV2 in animal species and the environment. Research on SARS-CoV2 molecular and biological characterisation. SARS-CoV2 surveillance and risk assessment, focused on the animal human interface. Coronavirus preparedness. |
| Impact | European-wide Coronavirus consortia, enrolement in to UK-ICN (Defra/BBSRC) |
| Start Year | 2021 |
| Description | NCS-Protect COVID theme 5 Mechanisms of Transmission |
| Organisation | Health and Safety Executive (HSE) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Asymptomatic/mild SARS-COV-2 skin-skin & bio-aerosols transmission, pig skin and ferret models. |
| Collaborator Contribution | HSE are the programme co-ordinators Transmission and Environment (also known as PROTECT) Led by Andrew Curran (Health and Safety Executive) improves understanding of COVID-19 virus transmission in different settings and environments. Imperial are the theme 5 leads Experimental Infections of Human and Animals to Characterize SARS CoV 2 transmission Led by Wendy Barclay Sharing of virus biobank materials www.hdruk.ac.uk/covid-19/covid-19-national-core-studies/ The COVID-19 National Core Studies are a crucial part of the UK's ongoing pandemic response. They are enabling the UK to use health data and research to inform both our near and long-term responses to COVID-19, as well as accelerating progress to establish a world-leading health data and research infrastructure for the future. |
| Impact | NCS-Protect Annual Conference presentation, Nov 2021 Microbiology Society April, 2022 Annual conference abstracts |
| Start Year | 2021 |
| Description | NCS-Protect COVID theme 5 Mechanisms of Transmission |
| Organisation | Imperial College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Asymptomatic/mild SARS-COV-2 skin-skin & bio-aerosols transmission, pig skin and ferret models. |
| Collaborator Contribution | HSE are the programme co-ordinators Transmission and Environment (also known as PROTECT) Led by Andrew Curran (Health and Safety Executive) improves understanding of COVID-19 virus transmission in different settings and environments. Imperial are the theme 5 leads Experimental Infections of Human and Animals to Characterize SARS CoV 2 transmission Led by Wendy Barclay Sharing of virus biobank materials www.hdruk.ac.uk/covid-19/covid-19-national-core-studies/ The COVID-19 National Core Studies are a crucial part of the UK's ongoing pandemic response. They are enabling the UK to use health data and research to inform both our near and long-term responses to COVID-19, as well as accelerating progress to establish a world-leading health data and research infrastructure for the future. |
| Impact | NCS-Protect Annual Conference presentation, Nov 2021 Microbiology Society April, 2022 Annual conference abstracts |
| Start Year | 2021 |
| Description | OH-EJP COVRIN |
| Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | SARS-CoV-2 Research Integration and preparedness (COVID19JIP) COVRIN. SARS-CoV-2 emergence, risk assessment and preparedness |
| Collaborator Contribution | UK contribution to EU Horizon 2020 programme https://onehealthejp.eu/jip-covrin/ |
| Impact | COVIRN annual and WP meetings MVNA Workshop contributions Sept 2021 EPIZONE abstract submitted May 2022 Defra SARS-CoV-2 Science Day Feb 2021 MVNA JMM Editorial / Review June 2022 COVRIN Final Meeting Decemver 2022 |
| Start Year | 2020 |
| Description | UK International Coronavirus Network |
| Organisation | University of Liverpool |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Co-director of UK-ICN https://www.liverpool.ac.uk/health-and-life-sciences/research/uk-international-coronavirus-network/ |
| Collaborator Contribution | Start-up meeting Nov 2021 Organisation of workshops and meetings - Oceania Sept 2022, Livestock & Pets 2023 Annual General Meeting 2022, 2023 |
| Impact | Meeting report |
| Start Year | 2021 |
| Description | 'SARS-CoV-2 Delta variant protects against homologous and heterologous variant re-infection and transmission in a mild/asymptomatic ferret model' at the UK-ICN Livestock, Wildlife, Companion animal conference, 25th-26th May 2023 Belfast. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Oral presentation at the UK-ICN Livestock, Wildlife, Companion animal conference, 25th-26th May 2023 Belfast Media and Industry coverage by CEVA, including YouTube video shared on social media platforms - LinkedIn and Twitter (X) WOAH gap analyses / road map carried out during the meeting, to be published in 2024. https://www.youtube.com/watch?v=JMHKKitJirM |
| Year(s) Of Engagement Activity | 2023 |
| Description | 'SARS-CoV-2 Delta variant protects against longitudinal homologous and heterologous variant re-infection and transmission in a mild/asymptomatic ferret model' at the Microbiological Society Conference 17-20 April 2023. Abstract available : Annual Conference 2023 | Microbiology Society P777, page 785. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Poster presentation at at the Microbiological Society Conference annual conference 17-20 April 2023, Birmingham International Convention Centre. |
| Year(s) Of Engagement Activity | 2023 |
| Description | 3. Abstract submitted for the Microbiological Society conference, Aerosols and microbiology: connecting disciplines in the post-pandemic era 4-6June 2024. 'Modelling the generation of bioaerosols during SARS-CoV-2 infection in ferrets: Implications for virus transmission'. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Abstract submitted for the Microbiological Society conference, Aerosols and microbiology: connecting disciplines in the post-pandemic era 4-6June 2024. 'Modelling the generation of bioaerosols during SARS-CoV-2 infection in ferrets: Implications for virus transmission'. https://microbiologysociety.org/event/society-events-and-meetings/aerosols-and-microbiology.html Chair / moderate Session 4: Inhalational and Transmission Models, and Treatment |
| Year(s) Of Engagement Activity | 2024 |
| Description | APHA Virologist co-directing the new UK - International Global Coronavirus Network (UK-ICN), blog |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | APHA Science blog https://aphascience.blog.gov.uk/2021/09/23/international-global-coronavirus-network/ |
| Year(s) Of Engagement Activity | 2021 |
| Description | International Coronavirus Networks Collection |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | https://www.microbiologyresearch.org/content/international-coronavirus-networks-collection-nbsp US Food and Drug Administration (FDA), the UK International Coronavirus Network (UK-ICN) - Biotechnology and Biological Research Council (BBSRC) and the Department of Environment, Food and Rural Affairs (DEFRA), the Biosafety Level 4 Zoonotic Laboratory Network (BSL4ZNet), the Commonwealth Scientific and Industrial Research Organisation (CSIRO) collective bring together findings and lessons learnt for science foresight perspectives on Coronaviruses into our future. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Northampton High School - Women in Science |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | British Science Week schools outreach talk, 20 young students interested in science and animal-human health |
| Year(s) Of Engagement Activity | 2022 |